Karine Titier

A liquid chromatography-tandem mass spectrometry method is described for the blood determination of selective serotonin reuptake inhibitors (fluoxetine, paroxetine, sertraline, fluvoxamine, and citalopram), serotonin noradrenaline reuptake inhibitors (milnacipram and venlafaxine), a noradrenergic and specific serotoninergic antidepressant (mirtazapine) and five of their active metabolites (norfluoxetine, desmethylcitalopram, didesmethylcitalopram, desmethylvenlafaxine, and desmethylmirtazapine). After a liquid-liquid extraction from blood, the compounds and the internal standard (methylrisperidone) were eluted on a XTerra^® RP18 column with a gradient of acetonitrile/ammonium formate buffer 4 mmol/L pH 3.2. They were then detected by electrospray ionization mass spectrometry with multiple reaction monitoring mode. The calibration curves were linear over the range 5–500 ng/mL (20–2000 ng/mL for venlafaxine and desmethylvenlafaxine). The limit of quantification was set at 5 ng/mL for each compound (except for venlafaxine and desmethylvenlafaxine: 20 ng/mL). The bias were lower than 12%. Intraday and interday precisions, expressed as variation coefficient, were lower than 11%. The extraction recoveries were between 70 and 90% except for desmethylmirtazapine, desmethylvenlafaxine, milnacipram, and didesmethylcitalopram. This specific and sensitive method allows management of intoxication and is suitable for the routine determination of antidepressants in forensic investigations.

Here we describe a liquid chromatography-tandem mass spectrometry method for the blood determination of tricyclic antidepressant drugs (amitriptyline, clomipramine, trimipramine, and imipramine, doxepin, mianserin, maprotyline, dosulepine, amoxapine), their active metabolites (desipramine, nortriptyline, demethylclomipramine, and nordoxepin), and monoamine oxidase inhibitors (toloxatone and moclobemide). A nontricyclic antidepressant (viloxazine) and two other anxiolytic drugs (buspirone and hydroxyzine) that could be encountered in toxicology have been included to this method. After a liquid-liquid extraction from blood, the compounds and their internal standard (methylrisperidone) were eluted on a XTerra^® RP18 column with a gradient of acetonitrile/ammonium formate buffer 4 mmol/L (pH 3.2). They were then detected by electrospray ionization mass spectrometry with multiple reaction monitoring mode. The calibration curves were linear over the range 5–100 ng/mL. The limit of quantification was 2 ng/mL for each compound. The bias were lower than 10%. Intraday and interday precisions, expressed as variation coefficient, were lower than 13 %. The extraction recoveries were between 60 and 80% except for moclobemide, viloxazine, and toloxatone (10–60%). This specific and sensitive method allows management of intoxication and is suitable for the routine determination of antidepressants in forensic investigation.

Imatinib, also known as Gleevec or Glivec, is a selective tyrosine kinase inhibitor currently used for the treatment of Philadelphia chromosome-positive chronic myeloid leukemia (CML) and for other malignant pathologies. We have developed a LC-MS-MS [corrected] method that could be used for imatinib therapeutic drug monitoring in plasma. After a liquid-liquid extraction, the imatinib and its deuterated internal standard were eluted on an XTerra RP18 column with a gradient of acetonitrile-ammonium formiate buffer 4 mmol/L, pH 3.2. Imatinib was detected by electrospray ionization mass spectrometry with multiple reaction-monitoring mode. The calibration curves were linear over the range 10-5000 ng/mL. The limit of quantification was set at 10 ng/mL. The bias was lower than 8%. Intra-day and inter-day precisions were lower than 8%. The extraction recovery was higher than 90%. This method is simple, adapted to routine application, and allows accurate therapeutic monitoring of imatinib. It can be used to evaluate patient adherence to daily oral therapy, drug-drug interactions, or pharmacokinetic/pharmacodynamic relationships.

Syncope and sudden death are features of schizophrenia that can be attributed to ischaemic heart disease, the use of antipsychotics (because of proarrhythmia or other reasons such as pharyngeal...

A high-performance liquid chromatographic method is described for the determination of selective serotonin reuptake inhibitors (fluvoxamine, paroxetine, sertraline, fluoxetine, citalopram, mirtazapine), serotonin norepinephrine reuptake inhibitors (milnacipram, venlafaxine), a noradrenergic and specific serotoninergic antidepressant (mirtazapine), and five pharmacologically active metabolites (desmethylcitalopram, didesmethylcitalopram, norfluoxetine, O-desmethylvenlafaxine, desmethylmirtazapine). After a double-step liquid-liquid extraction, compounds are separated on a Symmetry® C8 column eluted with a gradient of acetonitrile-phosphate buffer 10 mM pH 3.8 and detected at 230 nm and 290 nm. Calibration curves were linear in the range 25 to 500 ng/mL (100-2000 ng/mL for venlafaxine and its metabolite). The limit of quantification was 25 ng/mL (100 ng/mL for venlafaxine and its metabolite). For all quality controls good accuracy was achieved (93% to 99.5%) with intraday and interday variation coefficients less than 12%. This method allows simple and rapid (run time 18 min) identification and quantification of the eight new antidepressants and five of their active metabolites. This method can be used for toxicologic purpose.